中文摘要：

目的：探讨氯沙坦对脂多糖（LPS）诱导的星形胶质细胞活化标志物胶质纤维酸性蛋白（GFAP）表达的影响,以及其机制是否与激活腺苷酸活化蛋白激酶（AMPK）有关。方法：将成年雄性昆明小鼠分为正常对照组、LPS模型组、氯沙坦给药组及氯沙坦与compound C合用组。侧脑室注射相同剂量LPS（24μg/d,每天1次,共2次）,以建立中枢神经炎症损伤模型;氯沙坦（0.5、1或5 mg·kg~（-1）·d~（-1））于LPS注射前14 d开始连续每日腹腔注射给药;AMPK抑制剂Compound C（10 mg·kg~（-1）·d~（-1））于LPS注射前2 d开始连续每日腹腔注射给药。在LPS末次注射后的第3天取各组小鼠的海马脑区组织,利用Western blot法检测GFAP、AMPK、p-AMPK、哺乳动物雷帕霉素靶蛋白（mTOR）和p-mTOR的蛋白水平。结果：2次LPS注射后可显著诱导GFAP在海马脑区的表达（P〈0.01）,而氯沙坦可浓度依赖地抑制LPS诱导的GFAP表达,当氯沙坦剂量为5 mg·kg~（-1）·d~（-1）时可显著抑制GFAP表达（P〈0.05）,同时,在该剂量下,氯沙坦显著提高了AMPK的磷酸化水平（P〈0.01）,但对mTOR的磷酸化水平无明显调节作用;而AMPK抑制剂Compound C可显著逆转氯沙坦对GFAP表达及AMPK磷酸化的调节作用（P〈0.05）。结论：氯沙坦可抑制LPS诱导的海马GFAP表达,该作用可能与其激活AMPK有关,但并不依赖于mTOR信号通路。

英文摘要：

AIM： To investigate the effects of losartan on lipopolysaccharide（ LPS）-induced glial fibrillary acidic protein（ GFAP） expression,and to determine whether adenosine 5 ＇-monophosphate（ AMP）-activated protein kinase（ AMPK） activation is involved in the mechanism. METHODS： Adult male KM mice were divided into control group,LPS model group,losartan treatment group,and losartan and Compound C co-treatment group. To establish a model of central nervous system inflammation,the mice received daily intracerebroventricular injection of LPS（24 μg/d） for 2 d.Daily losartan administration（0. 5,1 or 5 mg·kg~（-1）·d~（-1）,ip） initiated at 14 d prior to LPS injection. Compound C（10mg/kg,ip）,a selective AMPK inhibitor,started to be injected daily at 2 d prior to LPS injection. The hippocampal tissues in each group were isolated at 3 d after the last LPS injection,and then the protein levels of GFAP,AMPK,p-AMPK,mammalian target of rapamycin（ mTOR） and p-mTOR were determined by Western blot. RESULTS： Twice LPS injections significantly increased the expression of GFAP in the hippocampus（ P 0. 01）. Losartan inhibited LPS-induced GFAP expression in a concentration-dependent way,and losartan at 5 mg·kg~（-1）·d~（-1）significantly inhibited GFAP expression and AMPK activation（ P 0. 05）,but it had no obvious effect on mTOR activation. Furthermore,Compound C significantly reversed the effect of losartan treatment on LPS-induced GFAP expression and AMPK phosphorylation（ P 0. 05）.CONCLUSION： Losartan inhibits LPS-induced GFAP expression in the mouse hippocampus,and AMPK activation but not mTOR,is involved in the mechanism.